Sol-Gel Polymeric Stationary Phases for High-Performance Liquid Chromatography and Solid Phase Extraction:  Their Method of Making

ABSTRACT

A sol-gel sorbent or chromatography stationary phase is a particulate metal oxide gel containing polymeric segments uniformly distributed throughout the metal oxide gel. The metal oxide gel is an oxide from silicone or other metal oxide that can have one of the valence bonds attached to an organic group and the remainder occupied by oxygens that can be provided as an oxide or an alkoxide or aryl oxide of the polymeric segments. The particles are used for an SPE sorbent or as a packing for a reversed phase high-performance liquid chromatography (RP-HPLC), a normal phase high-performance liquid chromatography (NP-HPLC) column or a hydrophilic interaction liquid chromatography (HILIC) column.

CROSS-REFERENCE TO A RELATED APPLICATION

This application is a divisional of U.S. application Ser. No.15/634,487, filed Jun. 27, 2017, now U.S. Pat. No. 9,925,518, thedisclosure of which is hereby incorporated by reference in its entirety,including any figures, tables, or drawings.

BACKGROUND OF INVENTION

Stationary phase is the heart of chromatographic separation process. Dueto the absence of suitable common stationary phase immobilizationtechnique, gas chromatography and liquid chromatography utilizecompletely two different types of materials as the separation media:polymeric stationary phases for gas chromatography and monomericstationary phases for liquid chromatography. Immobilization ofstationary phase in gas chromatography is relatively simple andstraightforward and generally involves free radical cross-linking orchemical bonding technique. Unlike gas chromatography, stationary phasein liquid chromatography makes direct contact with the mobile phase inits liquid state, and hence requires strong chemical anchorage with thesubstrate to prevent from washing away with the mobile phase.

In order to prevent from losing the stationary phase by dissolving inthe mobile phase, reversed phase and normal phase high-performanceliquid chromatography (RP-HPLC, NP-HPLC) were evolved with exclusivelydifferent combinations of stationary phase and mobile phase. RP-HPLCutilizes non-polar stationary phases and polar mobile phases, whereasNP-HPLC utilizes polar stationary phases and non-polar mobile phases.This artificial classification and exclusivity in stationaryphase/mobile phase selection substantially limit the power ofhigh-performance liquid chromatography. As such, a limited number ofmonomeric nonpolar stationary phases including C4, C8, C18, and C30 areused in RP-HPLC and diol, cyano, and amino polar monomeric ligands areused in NP-HPLC.

The strict restrictions in selecting stationary phase/mobile phasecombination has been relaxed to some extent after the introduction ofbonded phases where monomeric entities are chemically bonded to thesurface silanol groups present on silica substrate via silane chemistry.This approach of creating bonded phases has undoubtedly improved columnperformance, increased pH stability and prolonged its lifetime. Theadvent of the bonded phases led to a new direction in liquidchromatography known as hydrophilic interaction chromatography (HILIC).HILIC is a hybrid liquid phase separation approach that combines, to agreat extent, reversed phase and normal phase liquid chromatography.HILIC expands the separation power of liquid chromatography towardshighly polar analyte(s) that can't be dealt in normal phasechromatography due to the restricted choice of organic solvents (e.g.,hexane, isooctane, carbon tetrachloride) in which many of the polaranalytes are barely soluble. HILIC employs a polar stationary phase,such as silica, diol, amino, and cyano phases that are used for normalphase liquid chromatography and uses polar organic or organo-aqueoussolvent system as the mobile phase, such as those used in as in reversedphase liquid chromatography. Recently, introduction of bonded phases,such as diol, cyano, and amino ligands by bonding to a silica substratevia silane chemistry has allowed polar organic or organo-aqueous mobilephases to be used in hydrophilic interaction chromatography.Unfortunately, due to relatively weak bonding between the silicasubstrate and the organic ligands in these “so called” bonded phases,phase-bleeding often occurs upon exposure to polar organic solvents ororgano-aqueous solvent mobile phases, resulting in a continuous shift inchromatographic retention and selectivity change due to the exposure offree surface silanol groups of the silica support.

Supports for reversed phase high-performance liquid chromatography(RP-HPLC), normal phase high-performance liquid chromatography (NP-HPLC)or HILIC are silica particles coated with organic ligands via silanechemistry. As a result, only a very small portion of the stationaryphase contributes to retention and selectivity. The current bondedphases in RP-HPLC, NP-HPLC, and HILIC suffer from a number ofshortcomings: silica particles limit the loading of organic ligands;silane chemical bonding of target organic ligands to the substratesurface steric limits incorporation of organic ligands leaving manysurface silanol groups on the silica surface; and low carbon loading oforganic ligands results in chemical instability, particularly usingbasic solvents.

It is evident that regardless of the separation mode used inhigh-performance liquid chromatography, all stationary phases are basedon monomeric ligands with limited intermolecular interaction capabilityextended towards the analytes. For example, reversed phase stationaryphases interact with the analytes with weak London dispersion forces andnormal phases use limited dipole-dipole interaction/hydrogen bonding.Maximum separation/extraction potential of HPLC can only be utilizedwhen all possible intermolecular interactions including Londondispersion, dipole-dipole interaction, hydrogen bonding and π-π stackinginteractions are exercised.

Unlike high-performance liquid chromatography, solid phase extractionutilized silica particles coated with similar organic ligands as seen inHPLC stationary phases and therefore the choices are limited. Chemicalincorporation of various organic polymers into the sol-gel hybridinorganic-organic matrix would open up the possibility of creatinghundreds of novel sorbents with unique selectivity.

Organic polymers/macromeres/dendrimers/biopolymers represent a class ofcompounds possessing versatile surface chemistry with unique and richfunctionality. A successful immobilization technique such as sol-gelsynthesis can chemically incorporate these polymers in a 3D network ofmetal oxides e.g., silica, germania, titania backbone. All gaschromatographic stationary phases including polysiloxanes, polyethyleneglycols, phenylpolycarborane-siloxanes as well as other polymers notbeing used as gas chromatographic stationary phases can be readily usedas liquid chromatographic stationary phases if they possess at least oneterminal hydroxyl functional group. The effective incorporation offlexible organic polymer into rugged inorganic polymeric network maydramatically and synergistically expand the separation power of HPLC aswell as the extraction efficiency when used as solid phase extractionsorbents.

Stationary phases for RP-HPLC, NP-HPLC, and HILIC that overcome theinherent shortcomings of the current stationary phase manufacturingtechnology is the focus of the invention, where a sol-gel synthesisgenerates the support and the organic functionality simultaneously.Organic units can be included as hydroxyl terminated monomers andpolymers, and included by condensation with the sol-precursors, sol, orgel. A method of preparation that separately promotes hydrolysis ofsol-precursors to the sol and condensation of the sol to the gel iscarried out. Due to the strong chemical bonding between the 3D networkof metal oxide and organic monomer/polymer/macromere/dendrimer, theinvention opens up the possibility of eliminating artificialclassification of reversed phase and normal phase high-performanceliquid chromatography into a unified high-performance liquidchromatography that can use any polymeric stationary phase of desiredpolarity in combination with any organic solvent (nonpolar, mediumpolar, polar) or organo-aqueous solvent as the mobile phase to achievethe desired separation goal. In addition, the new approach will allowscientists to exploit high chemical stability (pH 1-13) and thermalstability of the sol-gel polymeric stationary phases and solid phasesorbents to maximize the separation potential as well as the extractionefficiency.

BRIEF SUMMARY

In an embodiment of the invention, a sol-gel extraction sorbent orchromatography stationary phase is particles of a metal oxide gelcontaining polymeric segments uniformly distributed throughout the metaloxide gel. The metal oxide gel is a gel formed by sol-gel hydrolysis andcondensation from one or more hydrolysable precursor where metal sitesin the gel have the structure R_(x)MO_((y-x)), where M is titanium,aluminum, zirconium, germanium, barium, gallium, indium, thallium,vanadium, cobalt, nickel, chromium, copper, iron, zinc, boron or anymixture thereof, x is 0 or 1, y is the valence of the metal, and R is C₁to C₆ alkyl or any C₆ to C₁₄ aryl or polyaryl group where the alkyl oraryl group optionally is functionalized with C₁ to C₂₀ alkyl, C₆ to C₁₄aryl, halo, hydroxy, alkoxy, aryloxy, or any other group incapable ofneutralizing an acidic or basic catalysts useful for faulting the metaloxide gel. The polymer or even an oligomer is selected from at least oneof silicones, polyethers, acrylates, methacrylates, polyesters, orpolyamides. In embodiments of the invention, the metal oxide gel is asilicon oxide gel where the polymeric segments arepolydimethylsilioxanes, polytetrahydrofurans, or polyethylene oxides.The sol-gel sorbent or chromatography stationary phase can includecapped MOH groups having non-functional or functional trialkylsilaneand/or an aryl dialkylsilane forming MOSi bonded groups.

Embodiments of the invention are directed to a method of preparing thesol-gel sorbents or chromatography stationary phases by providing: amixture of metal oxide precursors, water and, optionally, a solvent; apolymer comprising at least one hydroxyl group and, optionally, thesolvent or a second solvent; and an acid catalyst. Hydrolysis ispromoted by mixing the metal oxide precursors, water, polymer, acidcatalyst, and, optionally, solvent(s). Condensation to the metal oxidegel is promoted by adding a basic catalyst, optionally, a same ordifferent solvent, and, optionally, with warming. Upon crushing orgrinding the gel to form a particulate sol-gel sorbent or chromatographystationary phase according to claim 1.

In an embodiment of the invention, a reversed phase high-performanceliquid chromatography (RP-HPLC), a normal phase high-performance liquidchromatography (NP-HPLC) column or a hydrophilic interactionchromatography (HILIC) column is formed using the stationary phases thatare metal oxide gels containing polymeric segments uniformly distributedthroughout the metal oxide gels.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a flow chart for the preparation of a particulate solid phaseextraction sorbent via a sol-gel process involving a two-step acid-basecatalyzed sol-gel process, according to an embodiment of the invention.

FIG. 2A shows exemplary reaction equations to illustrate theincorporation of hydroxyl-terminated polydimethylsiloxane into a gelwith a hydrolyzed and partially condensed methyltrimethoxysilane (MTMS)derived sol, according to an embodiment of the invention.

FIG. 2B shows exemplary reaction equations to illustrate theincorporation of polyethylene glycol into a gel with a hydrolyzed andpartially condensed MTMS derived sol, according to an embodiment of theinvention.

FIG. 3A shows reaction schemes for the hydrolysis of tetramethoxysilane(TMOS) and MTMS.

FIG. 3B shows reaction schemes for the self- and cross-condensation ofTMOS and MTMS.

FIG. 4 is a table of the components combined into exemplary sols duringthe preparation of sorbents or normal phase chromatography supportsincluding hydroxyl terminated polydimethylsiloxane for absorbing orseparating non-polar analytes, according to embodiments of theinvention.

FIG. 5 is a table of the components combined into exemplary sols duringthe preparation of sorbents or normal phase chromatography supportsincluding polytetrahydrofuran (poly-THF), for absorbing or separatingmedium-polar analytes, according to embodiments of the invention.

FIG. 6 is a table of the components combined into exemplary sols duringthe preparation of sorbents or normal phase chromatography supportsincluding polyethylene oxide (PEO), for absorbing or separatinghighly-polar analytes, according to embodiments of the invention.

FIG. 7 is a table of compounds employed for evaluation of SPE sorbents,according to embodiments of the invention.

FIG. 8 is a bar chart of the percent extraction efficiencies for thecompounds of FIG. 7 for the SPE sorbents including hydroxyl terminatedpolydimethylsiloxane for absorbing non-polar analytes, according toembodiments of the invention.

FIG. 9 is a bar chart of the percent extraction efficiencies for thecompounds of FIG. 7 for the SPE sorbents including polytetrahydrofuran(poly-THF), for absorbing or separating medium-polar analytes, accordingto embodiments of the invention.

FIG. 10 is a bar chart of the percent extraction efficiencies for thecompounds of FIG. 7 for the SPE sorbents including polyethylene oxide(PEO), for absorbing or separating highly-polar analytes, according toembodiments of the invention.

DETAILED DISCLOSURE

In embodiments of the invention, reverse phase high-performance liquidchromatography (RP-HPLC), normal phase high-performance liquidchromatography (NP-HPLC) and hydrophilic interaction chromatography(HILIC) particulate stationary phases and solid phase extraction (SPE)sorbents are prepared by sol-gel chemistry where polymeric segments,with or without specific additional functional groups, are includedthroughout the gel comprising stationary phase. Although the gel can beused for the stationary phase for RP-HPLC, NP-HPLC or HILAC, the gel isoften referred to herein as only a stationary phase or as an SPE sorbentthroughout this specification, it should be understood that theparticulate gel can be employed in for any of a RP-HPLC stationaryphase, NP-HPLC stationary phase, HILIC stationary phase, or SPE sorbent.The process, as indicated in FIG. 1, involves the acid catalyzedhydrolysis of silanes, such as, but not limited to,alkyltrialkoxysilanes and tetraalkoxysilanes. A hydroxyl functionalpolymer, is included in the sol and subsequent condensation of theresulting silanols and hydroxyl functional groups of the polymer forms agel network that ultimately is the sol-gel sorbent or stationary phasewhen crushed to a desired particulate size. The polymer can be of anysize, including sizes that are sufficiently small to be characterized asoligomers. For example the polymer incorporated into the gel can havetwo to 10,000 repeating units.

The hydroxyl functional polymer, or precursors to the hydroxylfunctional polymer can be those with functional groups to interact witha non-polar, medium-polar, or highly-polar analyte of interest foranalysis in the fields of forensic investigation, safety monitoring, orother purposes. The polymers, or precursors thereto, can be silicones,polyethers, acrylates, methacrylates, polyesters, polyamides other vinyladdition polymers, or other condensation polymers. Mixtures of misciblepolymers can be used to form the gels. The polymers can be homopolymersor co-polymers, ter-polymers, or with multiple different repeating unitswhere repeating units can be in a block, graph, branched, or dendriticrelationship. Functional units within the polymers, or the polymersthemselves, can be in an organized relationship, such as, but notlimited to that of crown ethers, cryptand, cyclodextrins, fullerenes,nanotubes, or any other relationship where there is at least onehydroxyl functionality on the oligomeric or polymeric structure.Although throughout this specification the term polymer shall be used,it is to be understood that any oligomer, a small polymer of two to tenrepeating units, or one or more precursors to a hydroxyl functionaloligomer or polymer can be used.

The silicon oxide precursors that can be used are silanes with threeand/or four hydrolysable groups selected from hydrogen, alkoxy, hydroxy,halide, dialkylamino, or any combination thereof attached to the Siatom. Where there are three hydrolysable groups the remainingfunctionality can be any C₁ to C₂₀ alkyl or any C₆ to C₁₄ aryl orpolyaryl group where the alkyl or aryl group can be functionalized withC₁ to C₆ alkyl, C₆ to C₁₄ aryl, halo, hydroxy, alkoxy, aryloxy, or anyother functionality that would not neutralize the acidic or basiccatalysts used to form the sol-gel sorbent. Alternatively oradditionally, other metal oxide precursors can be used to the siliconoxide precursors, including oxides of titanium, aluminum, zirconium,germanium, barium, gallium, indium, thallium, vanadium, cobalt, nickel,chromium, copper, iron, zinc, boron or any mixture thereof. Whendifferent metal oxide precursors are used, the different precursors canbe combined before hydrolysis or hydrolysis or partial hydrolysis of theindividual metal oxide precursors can be carried out before combination.

The gel can be used as prepared after crushing or otherwise formingparticles. Optionally, after gelation and particle formation, silanecoupling agent, such as, but not limited to, trimethylchlorosilane, C₂to C₂₀ alkyldimethylchlorosilane, hexamethyldisilazane, bis-C₂ to C₂₀alkyltetramethysilazane, or C₁ to C₂₀ alkyldimethylaminodimethysilanecan be used to condense with all or any portion of the remaining silanolor hydroxy groups to form the final SPE sorbent, that contains fewer, ifany silanol or undesired hydroxy groups.

Sol-gel chemistry offers a unique bottom-up synthesis approach where,instead of using silica or other metal oxide particles as inert supportto attach functional groups to free silanol or MOH functionality on theparticle surface, a network of the stationary phases possessinghomogeneous distribution over the entire surface and within the gelnetwork with the organic ligands chemically bound throughout the gel'snetwork. The resulting metal oxide gel has excellent chemical, thermaland solvent resistance. This results in a greater number of readilyaccessible interaction sites for the components being separated bychromatography per unit mass of the stationary phase for separationand/or SPE sorbents for extraction of hydrophilic analytes. Theparticulate gels, according to an embodiment of the invention, allowrapid association with analytes with functionality of the stationaryphases or SPE sorbent. Separation power of the new stationary phase forchromatography and the sample capacity of a SPE sorbent can increaseover state of the art silica columns an order of magnitude or more. Byuse of alkyl derivatives of trialkoxysilanes or other metal oxideprecursors, in addition to or instead of tetraalkoxysilanes, an open gelstructure groups results that possessing few unreacted silanol.

According to embodiments of the invention, the sol-gel method is carriedout by hydrolysis of the sol-gel precursor(s) and polycondensation ofthe hydrolyzed precursor(s), to form a colloidal suspension, whichsubsequently turns into a 3D polymeric network. According to anembodiment of the invention, where an organic or inorganic polymer thatpossesses HO-terminal and/or HO-pendent groups is present in the solsolution, the organic polymers are randomly incorporated into the gelnetwork via polycondensation. The formation of the randomly incorporatedpolymers, such as polydimethylsiloxane (PDMS), polytetrahydrofuran(PTHF) or polyethylene glycol (PEG), is shown in FIGS. 2A and 2B,respectively. In this manner, the polarity and specific associations tothe chromatographic stationary phase or SPE sorbent can be specificallydesigned for a particular type of analyte or variety of analytes by thechoice of sol-gel precursors and inorganic or organic polymers forincorporation into the final gel network.

Under typical state of the art sol-gel processes with metal alkoxideprecursors, the rate and extent of hydrolysis and subsequentpolycondensation are dependent on the type and concentration of a singlecatalyst used in the process, and therefore, the catalyst determines thestructure and morphology of the resulting gel. Using an acid catalyst,such as, but not limited to, HCl, TFA, or acetic acid, hydrolysis of thealkoxide precursor proceeds at a faster rate than does condensation andresults in an extended or highly linearly connected gel; while,conversely, when catalyzed by a base, such as, but not limited to, NaOHor NH₄OH, polycondensation proceeds faster than hydrolysis, resulting ina highly branched and dense gel. In an embodiment of the invention, thesol-gel process is carried out by initially employing acid catalyst, togive a high proportion of hydrolysis, as shown in FIG. 3A for theexemplary hydrolysis of tetramethoxysilane (TMOS) andmethyltrimethoxysilane (MTMS), followed by base catalyst to assure highlevels of polycondensation, as illustrated in FIG. 3B for the self- andcross-condensation of hydrolyzed TMOS and MTMS. The stepwise use of acidcatalysis for hydrolysis and base catalysis for polycondensation resultsin a gel network with a distinct porous architecture that demonstratesunprecedented robustness with superior thermal, solvent, and chemicalstability. This gel structure is rendered even more porous by the use ofhydroxyl functionalized polymers.

According to an embodiment of the invention, many different inorganic ororganic polymers can be into the sol-gel network anchored by strongcovalent bonding throughout the gel. The selectivity for non-polarthrough highly polar analytes for the gel is defined by the nature ofthe polymer included in the sol solution for condensation withhydrolyzed sol-gel precursors. As a result, the gel materialsdemonstrate high resistance against high temperature, harsh chemicalenvironment, with pH stability that can range from 1-12, and significantswelling when exposed to organic solvents. The sol-gel formed gelparticles are useful for improved and new stationary phases in reversedphase liquid chromatography (RP-HPLC), normal phase liquidchromatography (NP-HPLC), stationary phases in hydrophilic interactionchromatography (HILAC), and solid phase extraction (SPE) sorbents. TheRP-HPLC, NP-HPLC, HILAC, and SPE sorbents, for example, but not limitedto sorbents in solid phase microextraction, can be used in the fields offood analysis, pharmaceutical analysis, environmental analysis,toxicological analysis, clinical analysis, and forensic analysis. Thesorbents can also be used for environmental remediation andantimicrobial and/or other protective coatings in food or pharmaceuticalpackaging.

Methods and Materials

Formulations for sorbents, normal phase chromatography stationaryphases, HILIC stationary phases, or SPE sorbents for separation andabsorbance of non-polar, medium-polar, and highly-polar analytes isgiven in FIGS. 4, 5, and 6, respectively. The TMOS and/or MTMS werecombined with the aqueous acid catalyst solution to promote hydrolysis,and subsequently the hydroxyl terminated PDMS, PTHF, or PEG. The basecatalyst solution was added to the hydrolyzed sol to promote gelation.Following gelation, the sol-gel sorbent monoliths were subjected toconditioning/aging at 50° C. for 24 hours. After aging, the sol-gelsorbent monoliths were crushed and washed with methylene chloride toremove any unreacted precursors, unbound polymers, reaction byproducts,and solvents from the sol-gel sorbent. The sol-gel sorbent gel was thendried under vacuum at 50° C. for overnight. The dried sol-gel sorbentparticles are then further crushed, milled, and screened to obtaindesired sol-gel sorbents of a desired particle size. Particles may betreated with silane coupling agents such as hexamethyldisilazane (HMDS)to cap residual silanol groups of the gel that is the SPE sorbents.

To examine the extraction efficiencies of the Gels as SPE sorbents, tencompounds, tabulated in FIG. 7, were examined in contrast to acommercial sorbent: Alltech® C18 SPE Sorbent for SPE sorbents designedfor the absorbance of non-polar, medium-polar, and highly-polaranalytes, as shown in FIGS. 8, 9, and 10, respectively. Regardless ofthe chemical make-up of the sol-gel sorbents, all outperformed theAlltech C18 solid phase extraction sorbent for nearly all analytes.

It should be understood that the examples and embodiments describedherein are for illustrative purposes only and that various modificationsor changes in light thereof will be suggested to persons skilled in theart and are to be included within the spirit and purview of thisapplication.

We claim:
 1. A method of preparing a sol-gel sorbent or chromatographystationary phase, comprising: providing a mixture of metal oxideprecursors, water and, optionally, a solvent; providing a polymercomprising at least one hydroxyl group and, optionally, the solvent or asecond solvent; providing an acid catalyst; mixing the metal oxideprecursors, the water, the polymer, the acid catalyst, and, optionally,the solvent and optionally, the second solvent to form a hydrolysismixture; providing a basic catalyst and optionally the solvent, thesecond solvent, or a third solvent; adding the basic catalyst andoptionally the solvent, the second solvent, or a third solvent to thehydrolysis mixture to form a gelation mixture; optionally, warming thegelation mixture; holding the gelation mixture until a gel forms; andcrushing or grinding the gel to form particles of a metal oxide gelcontaining polymeric segments uniformly distributed throughout the metaloxide gel, wherein the particles are a sol-gel sorbent or chromatographystationary phase.
 2. The method according to claim 1, wherein the metaloxide precursor comprises metal sites in the gel have the structureR_(x)MX_((y-x)) where M is titanium, aluminum, zirconium, germanium,barium, gallium, indium, thallium, vanadium, cobalt, nickel, chromium,copper, iron, zinc, boron or any mixture thereof, x is 0 or 1, y is thevalence of the metal, X is hydrogen, C₁ to C₄ alkoxy, hydroxy, halide,dialkylamino, or any combination thereof, and R is C₁ to C₆ alkyl or anyC₆ to C₁₄ aryl or polyaryl group where the alkyl or aryl groupoptionally is functionalized with C₁ to C₂₀ alkyl, C₆ to C₁₄ aryl, halo,hydroxy, alkoxy, aryloxy, or any other group incapable of neutralizingan acidic or basic catalysts useful for forming the metal oxide gel. 3.The method according to claim 2, wherein M is Si, X is C₁ to C₂ alkoxy,x is 0 or 1, and, R is methyl.
 4. The method according to claim 1,wherein the polymer comprises a silicone, a polyether, an acrylate, amethacrylate, polyesters, or a polyamide.
 5. The method according toclaim 4, wherein the polymer is polydimethylsiloxane,polytetrahydrofuran, or polyethylene glycol.
 6. The method according toclaim 4, wherein the polymer comprises a homopolymer, random copolymer,block copolymer, graft copolymer, or a dendrimer.
 7. The methodaccording to claim 1, wherein the metal oxide precursor comprises metalsites in the gel have the structure R_(x)MX_((y-x)) where M is titanium,aluminum, zirconium, geimanium, barium, gallium, indium, thallium,vanadium, cobalt, nickel, chromium, copper, iron, zinc, boron or anymixture thereof, x is 0 or 1, y is the valence of the metal, X ishydrogen, C₁ to C₄ alkoxy, hydroxy, halide, dialkylamino, or anycombination thereof, and R is C₁ to C₆ alkyl or any C₆ to C₁₄ aryl orpolyaryl group where the alkyl or aryl group optionally isfunctionalized with C₁ to C₂₀ alkyl, C₆ to C₁₄ aryl, halo, hydroxy,alkoxy, aryloxy, or any other group incapable of neutralizing an acidicor basic catalysts useful for forming the metal oxide gel; wherein thepolymer comprises a homopolymer, random copolymer, block copolymer,graft copolymer, or a dendrimer; and wherein the polymer comprises asilicone, a polyether, an acrylate, a methacrylate, polyesters, or apolyamide.